Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.

[New drugs in the treatment of chronic hepatitis C]. / Nuevos fármacos en el abordaje terapéutico de la hepatitis C.

OBJECTIVES: To analyze the efficacy and safety of the new direct antiviral agents (DAA) that will become the new therapeutic arsenal for the treatment of hepatitis C. METHODS: We carried out a research in the electronic database with the following criteria: phase II and III clinical trials (CT) published until February 2014. The Mesh term used was "chronic hepatitis C" and "therapy".Studies with boceprevir or telaprevir were excluded. For the analysis of efficacy, we evaluated the rate of Sustained Viral Response(SVR), and for the safety, side effects and safety-related discontinuations were analyzed. RESULTS: We included 24 CT that include associations with ribavirine(RBV) with or without peginterferon (PegINF) and associations of several DAA. The results associated of daclatasvir with PegINF and RBV have not been very successful. On the contrary, sofosbuvir presents activity in all viral genotypes . Sofosbuvir may be administered in free PegINF regimens. Around 90% of naïve patients achieve sustained virological response (RVS) and 80% in previously treated. In relation to second wave of NS3/4A protease inhibitors, simeprevir has achieved RVS in 90% of naïve patients and close to 80% in previously treated.The main combination of DAA were sofosbuvir and daclatasvir and sofosbuvir and ledipasvir. Both have achieved SVR in 100% of patients who previously had virological failure after receiving a protease inhibitor regimen with boceprevir or telaprevir. CONCLUSIONS: The new generation of AAD for the treatment of hepatitis C will lead to higher response rates in all subtypes of patients with lower complexity regimens and better tolerated.

Objetivos: Analizar la eficacia y seguridad de los nuevos agentesantivirales directos (AAD) que formaran parte del arsenal terapéuticopara el tratamiento de la hepatitis C.Método: Se realizó una búsqueda en la base de datos electrónicaPubMed, de artículos publicados Febrero de 2014 quecumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad denuevas generaciones de inhibidores de la proteasa (IP) frente alVHC, excluyendo con boceprevir y telaprevir.Resultados: Se incluyeron de 24 EC que incluyen asociacionesde AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvircon PegINF y RBV no han sido muy satisfactorios. Por el contrario,sofosbuvir es activo en todos los genotipos virales y permiteser administrado en regímenes libres de PegINF. Alrededordel 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuantoa la segunda generación de IP NS3/4A, destacar a simeprevir,con respuestas próximas al 90% en pacientes naïve y cercanasal 80% en pretratados. Entre las combinaciones de AAD evaluadas,sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzanel 100% de respuesta en no respondedores a triple terapiacon boceprevir y telaprevir.Conclusiones: Las nuevas generaciones de AAD frente al VHCvan a suponer un aumento de las tasas de curación en todoslos subtipos de pacientes, a través de regímenes más sencillosy mejor tolerados.

Nuevos fármacos en el abordaje terapéutico de la hepatitis C / New drugs in the treatment of chronic hepatitis C

Objetivos: Analizar la eficacia y seguridad de los nuevos agentes antivirales directos (AAD) que formaran parte del arsenal terapéutico para el tratamiento de la hepatitis C. Método: Se realizó una búsqueda en la base de datos electrónica PubMed, de artículos publicados Febrero de 2014 que cumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad de nuevas generaciones de inhibidores de la proteasa (IP) frente al VHC, excluyendo con boceprevir y telaprevir. Resultados: Se incluyeron de 24 EC que incluyen asociaciones de AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvir con PegINF y RBV no han sido muy satisfactorios. Por el contrario, sofosbuvir es activo en todos los genotipos virales y permite ser administrado en regímenes libres de PegINF. Alrededor del 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuanto a la segunda generación de IP NS3/4A, destacar a simeprevir, con respuestas próximas al 90% en pacientes naïve y cercanas al 80% en pretratados. Entre las combinaciones de AAD evaluadas, sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzan el 100% de respuesta en no respondedores a triple terapia con boceprevir y telaprevir. Conclusiones: Las nuevas generaciones de AAD frente al VHC van a suponer un aumento de las tasas de curación en todos los subtipos de pacientes, a través de regímenes más sencillos y mejor tolerados (AU)

Objectives: To analyze the efficacy and safety of the new direct antiviral agents (DAA) that will become the new therapeutic arsenal for the treatment of hepatitis C. Methods: We carried out a research in the electronic database with the following criteria: phase II and III clinical trials (CT) published until February 2014. The Mesh term used was “chronic hepatitis C” and “therapy”. Studies with boceprevir or telaprevir were excluded. For the analysis of efficacy, we evaluated the rate of Sustained Viral Response(SVR), and for the safety, side effects and safety-related discontinuations were analyzed. Results: We included 24 CT that include associations with ribavirine(RBV) with or without peginterferon (PegINF) and associations of several DAA. The results associated of daclatasvir with PegINF and RBV have not been very successful. On the contrary, sofosbuvir presents activity in all viral genotypes . Sofosbuvir may be administered in free PegINF regimens. Around 90% of naïve patients achieve sustained virological response (RVS) and 80% in previously treated. In relation to second wave of NS3/4A protease inhibitors, simeprevir has achieved RVS in 90% of naïve patients and close to 80% in previously treated. The main combination of DAA were sofosbuvir and daclatasvir and sofosbuvir and ledipasvir. Both have achieved SVR in 100% of patients who previously had virological failure after receiving a protease inhibitor regimen with boceprevir or telaprevir. Conclusions: The new generation of AAD for the treatment of hepatitis C will lead to higher response rates in all subtypes of patients with lower complexity regimens and better tolerated (AU)